日本免费黄色网址_国产又粗又大又爽大片精华液_午夜一区国产一级 片_深夜草莓视频下载APP_秋霞午夜理论2019理论中文_在线免费欧美成人亚洲_熟妇人妻av中文字幕_嫩草91久久精品中文字幕_四川小幺女国产一级毛片_波多野结衣无码在线

Accumulating body of evidence indicates that exposure to fine particulate matter (PM2.5) is closely associated with congenital heart disease in the offspring, but the underlying molecular mechanisms remain to be elucidated. We previously reported that extractable organic matter (EOM) from PM2.5 induces reactive oxygen species (ROS) overproduction by activating aromatic hydrocarbon receptor (AHR), leading to heart defects in zebrafish embryos. We hypothesized that endoplasmic reticulum (ER) stress might be elicited by the excessive ROS production and thereby contribute to the cardiac developmental toxicity of PM2.5. In this study, we examined the effects of EOM on endoplasmic reticulum (ER) stress, apoptosis, and Wnt signal pathway in zebrafish embryos, and explored their roles in EOM-induced heart defects. Our results showed that 4-Phenylbutyric acid (4-PBA), a pharmaceutical inhibitor of ER stress, significantly attenuated the EOM-elevated heart malformation rates. Moreover, EOM upregulated the expression levels of ER stress marker genes including CHOP and PDI in the heart of zebrafish embryos, which were counteracted by genetic or pharmaceutical inhibition of AHR activity. The ROS scavenger N-Acetyl-l-cysteine (NAC) also abolished the EOM-induced ER stress. We further demonstrated that both 4-PBA and CHOP genetic knockdown rescued the PM2.5-induced ROS overproduction, apoptosis and suppression of Wnt signaling. In conclusion, our results indicate that PM2.5 induces AHR/ROS-mediated ER stress, which leads to apoptosis and Wnt signaling inhibition, ultimately resulting in heart defects.Copyright ? 2022. Published by Elsevier Ltd.

原文鏈接：http://www.ncbi.nlm.nih.gov/pubmed/35948106